Long-Acting Lipoglycopeptides: “Lineless Antibiotics” for Serious Infections in Persons Who Use Drugs

Abstract

Background Injection drug use is associated with serious infections. Due to challenges with medical management of addiction, relapses and additional infections are common. Persons who use drugs (PWUD) are more likely to leave against medical advice before completing treatment, which could result in treatment failure. Prolonged intravenous (IV) antimicrobial therapy in PWUD may be complicated by concern for IV catheter misuse, sometimes requiring prolonged hospitalization. Ideal alternatives would provide the following: (1) high success rate; (2) reduced rate of medical complications; (3) improved safety profiles; and (4) improved cost-effectiveness. Long-acting lipoglycopeptides present such opportunity for treatment of serious Gram-positive infections. Methods We performed a system-wide, retrospective analysis of adults admitted to University of Colorado Health from September 2015 to June 2018 and treated with dalbavancin or oritavancin based on clinical judgment of their treating physicians. Results Fifty-six patients met inclusion criteria (17 PWUD vs 39 non-PWUD). The PWUD group were younger, healthier by Charlson comorbidity index, more likely insured by Medicaid, and admitted for conditions requiring longer treatment. Ten patients were lost to follow-up. Of the patients with follow-up, clinical failure was met in 1 PWUD patient (6%) and 6 non-PWUD patients (15%) (P = .413). The median hospital length-of-stay reduction was 20 days (interquartile range [IQR], 10–30 days) in PWUD vs 11 days (IQR, 9–14 days) in non-PWUD; P = .133. Estimated median savings were $40 455.08 (IQR, $20 900.00–$62 700.00) in PWUD vs $19 555.08 (IQR, $15 375.08–$23 735.08) in non-PWUD; P = .065. Conclusions Long-acting lipoglycopeptides may be equally effective as standard-of-care, present a safety advantage, and secure earlier discharge and significant cost-savings.

Advantages of Outpatient Treatment with Long‐Acting Lipoglycopeptides for Serious Gram‐Positive Infections: A Review

“…The oritavancin package insert lists similar adverse effects, with the addition of phlebitis and tachycardia at 2.5% 4 . In clinical trials, both agents showed a similar incidence of infusion‐related reactions; however, at our institution, rates of such reactions were higher with oritavancin 39 . With respect to serious adverse events (AEs)—which is of particular interest given the extra‐long half‐life of these agents—researchers reported that among 1778 enrolled patients in the dalbavancin group within phase II/III of the drug's ABSSSI clinical development program, 328 (18.4%) experienced treatment‐related AEs, 3 (0.2%) were serious treatment‐related AEs (compared with 9/1224 (0.7%) in the comparator group), and the duration of all treatment‐emergent AEs was similar (not longer) to the duration observed with the short‐acting comparators, despite dalbavancin's log half‐life 55 .…”

“…In yet another study, a savings of $1752.46–$6475.87/patient were projected with avoidance of hospitalization by administering oritavancin in the emergency departments 42 . Favorable real‐world experiences with the use of dalbavancin, including a report of significant cost savings, have recently been reported by a group of authors from Spain, and similar findings were corroborated by a U.S.‐based group in two retrospective studies evaluating both agents (savings of €3000/patient [~$3400/patient], $17,000/patient, and up to $40,000/patient in PWUD, in the three studies, respectively) 38,39,44 …”

“…In PWUD, these savings may be particularly pronounced. A follow‐up study at our institution, for example, showed median reductions in a hospital length‐of‐stay of 20 days compared to 11 days in non‐PWUD, with median cost savings of over $40,000 per patient 39 . Such considerations provide advantages in addition to accommodating the majority of patients' preferences for discharge from the hospital, possibly preventing instances where patients leave against medical advice with suboptimal therapy 43 .…”

“…Treatment success was obtained by oritavancin in the majority of these cases, including a 100% success rate for bacteremia. Oritavancin was demonstrated to have good tissue penetration in a rabbit bone model, and multiple cost‐effectiveness projections have suggested significant savings in ABSSSIs 36–42 …”

“…Savings from shorter hospitalizations and the resulting increase in hospital bed availability may offset the high initial medication acquisition costs of laLGPs and facilitate inpatient treatment of a higher number of patients within the same period 37–39 . In a study performed at our institution (UCHealth system), hospital length of stay was reduced by 9 days per patient treated with laLGP, corresponding to a projected health system cost saving of $17,204 per patient 38 .…”